Most of the studies which have assessed the effectiveness of antiretroviral therapy have looked at individuals infected with HIV subtype B - the most common subtype in north America and western Europe. Although many people assumed that antiretrovirals worked against other subtypes, there was little evidence to support this assumption.

However, two recent studies have provided proof that antiretroviral therapy is effective against non-B subtypes.

At the Royal Free Hospital, London, 50 people infected with non-B subtypes were compared with 50 matched subtype B patients from the clinic's patient database. All had started highly active antiretroviral therapy (HAART) and had subsequent CD4 cell count and viral load results recorded over a minimum of 24 weeks. There were no differences between the two groups in their average baseline viral load, the proportions who were treatment naﶥ, or in the regimens used. The groups differed only with respect to gender. Women were found more frequently in the non-B group than the subtype B group.

After an average follow-up period of 75 weeks, there were no differences in the proportions whose viral load fell either below 400 or 50 copies/ml, or in the speed at which these two markers were reached. Similarly, there was no difference in the average fall in viral load, in the average duration of response, or in the proportions who maintained a virological response after 48 weeks of treatment.

However, a comparison between European and non-European patients at St Mary's Hospital, London, found that non-Europeans were less likely to have undetectable viral load twelve months after starting HAART than European patients. Eighty-nine people with non-B subtypes, most of whom were Ugandan, were matched with 248 people infected with subtype B. The non-B group included a greater proportion of women than the subtype B group. After six months of HAART, viral load responses were similar across the two groups, with 81% having an undetectable viral load. However, by twelve months the groups had diverged: while 84% of the subtype B group had undetectable viral load at this point, only 56% of non-B patients were undetectable.

The St Mary's group suggest the differences they observed cannot be explained by differences in subtype response to anti-HIV drugs, given the similarity of viral load responses at the six month mark. Instead, they propose that poor adherence may explain the poorer response amongst non-B patients (though this was not measured within this study), and that there may be a need to reconsider the applicability of available adherence support measures to Africans and other non-Europeans.

Despite these findings, a test tube study from Ghana has shown that the prevalent subtype CRF02_AG is less susceptible to the unboosted protease inhibitors lopinavir, indinavir (Crixivan) and saquinavir (Invirase / Fortovase), and particularly nelfinavir (Viracept) than subtype B. However, this subtype was susceptible to ritonavir (Norvir) and amprenavir (Agenerase), leading the investigators to conclude that the use of ritonavir-boosed protease inhibitors, with the exception of nelfinavir, is still clinically useful in west Africa (Kinomoto 2005).

References

Frater AJ et al. Impact of baseline polymorphisms in RT and protease on outcome of highly active antiretroviral therapy in HIV-1-infected African patients. AIDS 15: 1493-1502, 2001.

Kinomoto M et al. HIV-1 proteases from drug-naﶥ west African patients are differentially less susceptible to protease inhibitors. Clin Infect Dis 41 (online edition), 2005.

Loveday C et al. Equivalence in virological responses to HAART in patients with HIV-1 subtype non-B infections: A case-controlled study (n = 100). Eighth Conference on Retroviruses and Opportunistic Infections, Chicago, abstract 525, 2001.